Paclitaxel-induced peripheral neuropathy is a common adverse effect during paclitaxel treatment resulting in sensory abnormalities and neuropathic pain during chemotherapy and in cancer survivors. Conventional therapies are usually ineffective and possess adverse effects. Here, we examined the effects of electroacupuncture (EA) on a rat model of paclitaxel-induced neuropathic pain and related mechanisms. EA robustly and persistently alleviated paclitaxel-induced pain hypersensitivities. Mechanistically, TLR4 (Toll-Like Receptor 4) and downstream signaling MyD88 (Myeloid Differentiation Primary Response 88) and TRPV1 (Transient Receptor Potential Vallinoid 1) were upregulated in dorsal root ganglion (DRGs) of paclitaxel-treated rats, whereas EA reduced their overexpression. Ca²⁺ imaging further indicated that TRPV1 channel activity was enhanced in DRG neurons of paclitaxel-treated rats whereas EA suppressed the enhanced TRPV1 channel activity. Pharmacological blocking of TRPV1 mimics the analgesic effects of EA on the pain hypersensitivities, whereas capsaicin reversed EA’s effect. Spinal astrocytes and microglia were activated in paclitaxel-treated rats, whereas EA reduced the activation. These results demonstrated that EA alleviates paclitaxel-induced peripheral neuropathic pain via mechanisms possibly involving suppressing TLR4 signaling and TRPV1 upregulation in DRG neurons, which further result in reduced spinal glia activation. Our work supports EA as a potential alternative therapy for paclitaxel-induced neuropathic pain.

Background: Complex regional pain syndrome type-I (CRPS-I) causes excruciating pain that affect patients’ life quality. However, the mechanisms underlying CRPS-I are incompletely understood, which hampers the development of target specific therapeutics. Methods: The mouse chronic post-ischemic pain (CPIP) model was established to mimic CRPS-I. qPCR, Western blot, immunostaining, behavioral assay and pharmacological methods were used to study mechanisms underlying neuroinflammation and chronic pain in spinal cord dorsal horn (SCDH) of CPIP mice. Results: CPIP mice developed robust and long-lasting mechanical allodynia in bilateral hindpaws. The expression of inflammatory chemokine CXCL13 and its receptor CXCR5 was significantly upregulated in ipsilateral SCDH of CPIP mice. Immunostaining revealed CXCL13 and CXCR5 was predominantly expressed in spinal neurons. Neutralization of spinal CXCL13 or genetic deletion of Cxcr5 (Cxcr5^−/−) significantly reduced mechanical allodynia, as well as spinal glial cell overactivation and c-Fos activation in SCDH of CPIP mice. Mechanical pain causes affective disorder in CPIP mice, which was attenuated in Cxcr5^−/− mice. Phosphorylated STAT3 co-expressed with CXCL13 in SCDH neurons and contributed to CXCL13 upregulation and mechanical allodynia in CPIP mice. CXCR5 coupled with NF-κB signaling in SCDH neurons to trigger pro-inflammatory cytokine gene Il6 upregulation, contributing to mechanical allodynia. Intrathecal CXCL13 injection produced mechanical allodynia via CXCR5-dependent NF-κB activation. Specific overexpression of CXCL13 in SCDH neurons is sufficient to induce persistent mechanical allodynia in naïve mice. Conclusions: These results demonstrated a previously unidentified role of CXCL13/CXCR5 signaling in mediating spinal neuroinflammation and mechanical pain in an animal model of CRPS-I. Our work suggests that targeting CXCL13/CXCR5 pathway may lead to novel therapeutic approaches for CRPS-I.

Background: Atlantoaxial rotatory subluxation (AARS) is a common cause of acquired painful torticollis in children. Conservative treatment is widely used, but high-quality randomized evidence for structured muscle-focused rehabilitation is limited. Musculoskeletal ultrasound, especially shear-wave elastography (SWE), can measure cervical muscle stiffness in a non-invasive way. This trial aims to test the efficacy and safety of joint mobilization combined with cervical resistance training in children with AARS. It will also examine whether ultrasound-based measures can detect treatment-related changes in cervical muscle stiffness. Methods: This is a single-center, assessor- and analyst-blinded, randomized controlled superiority trial with two parallel groups. Seventy children aged 2–18 years with clinically and radiologically confirmed AARS will be randomly assigned in a 1:1 ratio to joint mobilization plus cervical resistance training or joint mobilization alone. Both groups will receive treatment 3 times per week for 4 weeks. The primary outcome is affected-side sternocleidomastoid stiffness at week 4 measured by SWE and adjusted for baseline stiffness. Secondary outcomes include bilateral sternocleidomastoid and upper trapezius SWE parameters, pain intensity, cervical disability, cervical rotation range of motion, overall clinical efficacy, and recurrence-related outcomes. SWE outcomes will be assessed at baseline, week 2, and week 4. Pain and disability outcomes will be assessed at baseline, week 2, week 4, and at 3 and 6 months after treatment. Cervical rotation range of motion will be assessed at baseline, week 2, and week 4. Recurrence-related outcomes will be recorded at the 3- and 6-month follow-up visits. Discussion: This randomized controlled trial is designed to provide high-quality evidence regarding the effectiveness of joint mobilization combined with cervical resistance training for pediatric AARS. By incorporating musculoskeletal ultrasound as an objective assessment tool, the study aims to elucidate the relationship between cervical muscle mechanical properties and clinical outcomes. The findings may contribute to the development of standardized, muscle-focused conservative treatment strategies for children with AARS. Trial registration: International Traditional Medicine Clinical Trial Registry ( ITMCTR2025002448 ), registered on 27 October 2025.